Table of Content

31 March 2020, Volume 25 Issue 3

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Liver Fibrosis & Cirrhosis

Study on the current status of Direct-acting antiviral Treatment in Chinese patients with HCV-related liver cirrhosis

ZHUANG Yan, LU Jie, XIE Qing, LIN Lan-yi.

2020, 25(3):  249-253. 

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Objective To investigate the current treatment situation and explore the impact factors for short-term prognosis after direct-acting antiviral (DAA) therapy in Chinese patients with hepatitis C virus (HCV)-related liver cirrhosis.Methods Patients with HCV-related liver cirrhosis who visited the clinical center from Jan 2015 to Nov 2019 at the Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University were enrolled. Clinical characteristics and DAA treatment status were collected according to current international practice guidelines. Impact factors for treatment responses and short-term prognosis after treatment were analyzed in the followed-up populations. Results A total of 161 patients with HCV-related liver cirrhosis were included, among which 149 received DAA therapies, 122 compensated and 27 decompensated. Baseline charactersitics, including age, gender, HCV genotype and previous interferon (IFN) exposure history, were comparable between compensated and decompensated groups. Excellent treatment responses along with extremely low incidences of adverse events were achieved in both groups (both P<0.05). Rates of SVR12 and SVR24 were 99.17% vs. 96.25% (P=0.325) and 96.64% vs. 92.0% (P=0.614) in compensated and decompensated groups. Significant poorer prognosis was demonstrated in patients with decompensated cirrhosis when compared to compensated cirrhosis (50% vs. 13.75%,P=0.000). The area under the receiver operating characteristic curve revealed decompensated cirrhosis before the initiation of treatment to be the only predictive factor for short-term prognosis after DAA treatment (HR 6.765,95% Cl:2.866-15.969,P=0.000).Conclusion Decompensated cirrhosis before the initiation of treatment was an independent impact factor for short-term prognosis after DAA treatment in HCV-related cirrhotic patients.

Terlipressin in the treatment of type one hepatorenal syndrome: a systematic review and meta-analysis

DONG Xin-xin, WANG Hai-qing, WANG Xing-chun.

2020, 25(3):  254-259. 

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Objective Hepatorenal syndrome is a fatal complication of the decompensated stage of cirrhosis. Terlipressin is the most widely used treatment method, however, the therapy effects remains inconsonant. We aim to systematically assess the safety and efficacy of terlipressin in the treatment type 1 hepatorenal syndrome.Methods We conducted a systematic review and meta-analysis. Randomized controlled trials form databases such as PubMed and Embase involving terlipressin for hepatorenal syndrome were included in a systematic literature search. Two authors independently assessed the studies for inclusion and extracted the data. A meta-analysis was conducted to estimate the safety and efficacy of terlipressin for hepatorenal syndrome. Results A total of 13 randomized controlled trials including 746 patients were included. These studies included 5 studies comparing with placebo, 6 studies comparing with noradrenaline, one comparing with dopamine and one comparing with octreotide. The total hepatorenal syndrome reverse rate was 33.7% and the total mortality was 60.1%. Terlipressin had greater hepatorenal syndrome reverse (RR=2.13, 95%CI: 1.26-3.61, P=0.005, I² =51%) and more adverse events (RR=2.05, 95%CI: 1.36-3.09, P=0.0006, I² =0%) than the control group in the management of type 1 hepatorenal syndrome. The subgroup analysis showed that terlipressin had superiority comparing to placebo, but the safety and efficacy was similar when comparing with norepinephrine.Conclusion Terlipressin was one of the most effective drugs for management of type 1 hepatorenal syndrome.

Predictive value of hepatic hemodynamics ultrasonic parameters combined with peripheral blood vWF-Ag in esophageal varices hemorrhage in patients with liver cirrhosis

CHENG Jing, XU Lu, PENG Su-qiong.

2020, 25(3):  260-263. 

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Objective To investigate predictive value of hepatic hemodynamics ultrasonic parameters combined with peripheral blood von Willebrand factor antigen (vWF-Ag) for esophageal varices hemorrhage (EVH) in patients with liver cirrhosis.Methods From December 2015 to December 2018, 80 cases of cirrhosis, 80 cases of cirrhosis combined with EVH patients and 80 healthy individuals in our hospital were enrolled, and set as cirrhosis group, cirrhosis & EVH group, and control group, respectively. Various indexes were compared between groups, including hepatic hemodynamics ultrasonic parameters, as well as the serum vWF-Ag levels. The correlation of hemodynamics ultrasonic parameters and peripheral blood vWF-Ag level in cirrhosis combined with EVH patients was analyzed. Results Significant differences were found in the levels of PVD[(1.25±0.20), (1.52±0.25), (0.78±0.15)], PV-CI[(0.08±0.03), (0.13±0.03), (0.05±0.01)], PVAT[(19.88±4.59), (23.34±3.68), (13.19±3.02)], PVV[(18.13±4.38), (15.88±4.23), (20.20±4.16)], HVAT[(20.35±5.19), (16.77±2.66), (23.96±5.56)], IHCT[(9.53±2.55), (6.48±1.90), (11.12±2.93)], HV-DI[(0.62±0.12), (0.75±0.13), (0.51±0.11)] and serum vWF-Ag [(150.15±19.61), (211.09±50.83), (90.33±10.28)]in the 3 groups cirrhosis group, cirrhosis & EVH group, and control group (P<0.05). With the increase of the EVH severity (mild, moderate, severe), the levels of PVD[(1.38±0.08), (1.50±0.16), (1.61±0.23)], PV-CI[(0.12±0.04), (0.14±0.03), (0.16±0.05)], HV-DI[(0.72±0.09), (0.78±0.12), (0.84±0.15)], PVAT[(21.11±3.01), (23.45±4.23), (25.67±4.92)]and serum vWF-Ag[(206.45±35.43), (225.32±50.67), (256.30±59.62)]in patients with cirrhosis were increased, meanwhile, the PVV[(16.88±3.48), (14.33±2.12), (12.56±1.87)], HVAT[(18.45±2.68), (16.34±2.22), (13.26±1.08)]and IHCT[(6.29±1.76), (6.01±1.46), (5.91±1.03)]were decreased (P<0.05). Serum vWF-Ag levels in patients with cirrhosis and EVH were positively correlated with PVD, PV-CI, HV-DI and PVAT (P<0.05), and negatively correlated with PVV, HVAT and IHCT (P<0.05). The diagnostic efficacy of hepatic hemodynamics ultrasonic parameters combined with vWF-Ag in patients with cirrhosis with EVH was significantly better than single detection (P<0.05).Conclusion Predictive value of hepatic hemodynamics ultrasonic parameters combined with peripheral blood vWF-Ag is certain for cirrhosis combined with EVH patients, which is worthy of clinical promotion.

Liver Cancer

Application of indocyanine green excretion test and liver stiffness measurement before surgery of hepatocellular carcinoma

XU Xiao-luan, MENG Fan-kun, ZHENG Ying, SUN Li-juan, LI Xin.

2020, 25(3):  264-266. 

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Objective To evaluate the hepatic reserve function of patients with primary hepatocellular carcinoma (HCC) by indocyanine green (ICG) retention test before resection, to predict postoperative hepatic dysfunction, and to analyze the relationship between postoperative liver function recovery and preoperative liver stiffness measurement (LSM) value.Methods A total of 64 patients with HCC who underwent selective surgeries in our hospital from December 2015 to June 2017 were enrolled. All subjects accepted preoperative ICG retention test, ICG 15-minute retention (ICG-R15), ICG-R10, ICG-R5, effective blood flow and ICG elimination rate (ICGK) were recorded. All subjects were examined by Fibroscan-502 to obtain the LSM values. Biochemical indexes of liver function were detected to confirm the Child-Pugh classification. The recovery of liver functions was analyzed after the operation. Results ① Among the 64 patients, there were 53 cases of Child-Pugh A and 11 cases of Child-Pugh B. According to the classification of liver function, statistical analysis showed that there were significant differences between the 2 groups in ICG-R15, ICG-R10, ICG-R5, effective blood flow, ICGK, preoperative alanine aminotransferase (ALT), preoperative aspartate aminotransferase (AST), cholinesterase, total bilirubin and direct bilirubin (P<0.05). ② According to the ICG-R15 values, they were divided into 3 groups: less than 10%, between 10% and 20%, more than or equal to 20%. The number of cases in each group was 38, 11 and 15, respectively. There were 7, 4 and 8 cases who had postoperative liver dysfunction in the 3 groups, the incidence was 18.4%, 36.4% and 53.3%, respectively. There was significant difference among the 3 groups (P<0.05). ③ In the Child-Pugh A group, R15 was associated with preoperative ALT, preoperative AST, cholinesterase, total bilirubin, and direct bilirubin. The correlation coefficients were 0.361, 0.486, -0.526, 0.41, and 0.327, respectively. ④ The difference of preoperative LSM value between the liver dysfunction and the non-hepatic dysfunction groups was statistically significant (P<0.05).Conclusion The ICG retention test and LSM can be used to evaluate preoperative liver reserve function in patients with primary HCC and to predict the risk of postoperative liver dysfunction.

Characteristics of intestinal microecological structure changes in patients with hepatocellular carcinoma

SUN Liang, ZHOU Xuan, LIU Gui-zhi, LIN Mao-rui, LI Ming-you, CAO Dong-lin.

2020, 25(3):  267-269. 

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Objective To detect the characteristics of intestinal microecological structure changes in patients with hepatocellular carcinoma.Methods 87 patients with hepatocellular carcinoma were enrolled in this study. Another 80 healthy persons were taken as control. The microbial genomic was prepared for high throughput sequencing by Illumina platform. Results There was no significant difference in α diversity between hepatocellular carcinoma group and control group (P>0.05). The percentage of bacteroidetes and proteobacteria in hepatocellular carcinoma group was 56.41±4.63% and 9.26±1.82%, which was significant higher than that of 53.32±4.22% and 7.42±1.16% in control group(P<0.05 and P<0.01). The percentage of firmicutes and actinobacteria in hepatocellular carcinoma group was 32.62±3.75% and 0.34±0.05%, which was significant lower than that of 37.25±4.13% and 0.62±0.11% in control group(P<0.05 and P<0.01). The percentage of bacteroides and H.hepaticus in hepatocellular carcinoma group was 50.83±4.15% and 11.35±1.87%, which was significant higher than that of 42.45±3.84% and 8.52±1.71% in control group(P<0.01). The percentage of bifidobacterium and clostridium in hepatocellular carcinoma group was 21.13±3.64% and 10.44±1.25%, which was significant lower than that of 28.54±4.13% and 14.28±1.52% in control group(P<0.01).Conclusion The proportion of bacteroidetes, proteobacteria, bacteroides, and H.hepaticus in patients with hepatocellular carcinoma was significantly higher than that of control group. The proportion of firmicutes, actinobacteria, bifidobacterium and clostridium in patients with hepatocellular carcinoma was significantly lower than that of control group.

The value of CT perfusion imaging in the evaluation of liver reserve function before TACE intervention on liver cancer

YANG Huai-long, LEI Ting.

2020, 25(3):  270-272. 

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Objective To investigate the value of computed tomographic (CT) perfusion imaging in the evaluation of liver reserve function before transcatheter arterial chemoembolization (TACE) intervention on liver cancer.Methods A total of 68 patients with primary liver cancer admitted to our hospital from January to February 2018 were enrolled. All patients underwent CT perfusion imaging 3 days before TACE. The hepatic arterial perfusion (HAP), portal venous perfusion (PVP), total liver perfusion (TLP) and hepatic arterial perfusion index (HAPI) were compared between normal liver tissue and tumor tissue, among patients with different Child-Pugh grades, and the correlation between perfusion parameters and Child-Pugh classification was analyzed. Results The HAP and HAPI of normal liver tissue were (30.10 ± 8.69) ml/min/100 ml and (22.01 ± 5.03)%, respectively, which were significantly lower than those of tumor tissue[(81.47 ± 19.86) ml/min/100 ml, (69.85 ± 15.41)%, P<0.05]. The PVP and TLP were (80.52 ± 18.27) ml/min/100 ml and (148.10 ± 31.11) ml/min/100 ml, respectively, which were significantly higher than those of tumor tissue [(40.01 ± 9.88) ml/min/100 ml, (123.10 ± 26.49) ml/min/100 ml, P<0.05]. The HAPI of Child-Pugh grade A patients was significantly lower than that of grade B patients, and the PVP and TLP of grade A patients were significantly higher than those of grade B patients (P<0.05). Spearman correlation analysis showed no significant correlation between the HAP and Child-Pugh classification (r=0.119, P=0.367). The HAPI was positively correlated with Child-Pugh classification (r=0.442, P=0.002). The PVP and TLP were negatively correlated with Child-Pugh classification (r=-0.550, P<0.001; r=-0.489, P<0.001).Conclusion CT perfusion imaging can quantitatively reflect the hemodynamic changes of patients with different Child-Pugh grades, and evaluate the liver reserve function of patients, which can provide reference for preoperative evaluation of TACE and prediction of surgical outcomes.

Dynamic changes of TLR4 and intestinal flora in the progression of primary liver cancer and its relationship with prognosis

WANG Yu, XU Da-feng, ZHOU Kai-lun, WU Jin-cai, DING Yi-chao, GU Hai-qiang, XIE Ming-wei, LIN Ming-hua.

2020, 25(3):  273-276. 

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Objective To investigate the dynamic changes of Toll-like receptor 4 (TLR4) and intestinal flora in the progression of primary liver cancer, and to analyze their relationship with prognosis.Methods 100 patients with chronic hepatitis B (HBV), 80 patients with cirrhosis and HBV, and 60 patients with hepatocellular carcinoma and HBV were enrolled as subjects. They were named HBV group, cirrhosis group and liver cancer group, and matched with age and gender. One hundred healthy subjects were used as a control group. The expression of TLR4 on the surface of peripheral blood mononuclear cells was detected by flow cytometry. Fresh feces were collected from each group, and the distribution of intestinal flora was detected. The relationship between the two groups was analyzed. The expression of TLR4 and the distribution of intestinal flora in peripheral blood mononuclear cells of each group were compared, and the relationship between the expression of TLR4 and the prognosis of liver cancer patients was analyzed. Results The positive rates of CD14⁺TLR4⁺ monocytes in the peripheral blood of the control group, HBV group, liver cirrhosis group and liver cancer group were gradually increased, which were (34.92±4.79)%, (41.92±7.46)%, (49.21±8.83)%, and (57.62±10.58)% respectively, the difference between the four groups was statistically significant (F=78.624, P=0.000). The content of bifidobacteria in the control group, HBV group, liver cirrhosis group and liver cancer group decreased sequentially as (10.73±2.91) log CFU/g, (8.15±2.04) log CFU/g, (6.33±1.32) log CFU/g, and (5.21±0.87) log CFU/g, the difference between the four groups was statistically significant (F=15.932, P=0.000); the content of enterococci in the control group, HBV group, cirrhosis group and liver cancer group increased in turn, respectively (4.91±0.78) log CFU/g, (6.44±1.29) log CFU/g, (8.11±2.08) log CFU/g and (10.21±2.77) log CFU/g, the difference between the four groups was statistically significant (F= 12.372, P=0.000). According to Pearson correlation analysis, the expression of TLR4 on the surface of monocytes was negatively correlated with Lactobacillus and Bifidobacteria (P<0.05), and the correlation coefficients were -0.643 and -0.672 respectively. It was positively correlated with Enterococcus and Escherichia coli. (P<0.05), the correlation coefficients were 0.771 and 0.734 respectively. During the follow-up of 1 year, 18 of the 60 patients with liver cancer recurred and 15 died. The positive rates of CD14⁺TLR4⁺ monocytes in peripheral blood in relapsed and non-relapsed patients were (59.32±9.17)% and (55.21±5.23)%, respectively, and the difference was statistically significant (t=2.200, P=0.032). The positive rates of CD14⁺TLR4⁺ monocytes in peripheral blood of the deceased and survivors were (61.04±10.23)% and (53.29±8.11)%, respectively, and the difference was statistically significant (t=2.998, P=0.004). Compared with non-recurring and survivors, the content of bifidobacteria and lactobacilli in relapsed and deceased patients was significantly reduced, but the contents of Enterococcus and Escherichia coli were significantly increased, the difference was statistically significant (P<0.05).Conclusion TLR4 can promote the progression of HBV to liver cancer, which is significantly correlated with the changes of intestinal flora. Both of them have certain value in the prognosis monitoring of liver cancer.

Viral Hepatitis

The study on mechanism of prostaglandin E2 promoting replication of hepatitis B virus

HUANG Shan-shan, ZHAO Jing-ya, CHEN Jie, YANG Yang.

2020, 25(3):  277-281. 

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Objective To investigate the effect of prostaglandin E2 (PGE2) on hepatitis B virus (HBV) replication and T cell function.Methods The concentrations of PGE2 in serum of chronic hepatitis B (CHB) patients and healthy persons (HP) were measured by enzyme-linked immunosorbent assay. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum of patients with high or low levels of PGE2 were detected by kit,according to the instructions from the manufacturers. Flow cytometry was used to detect the function of cluster of differentiation 8⁺T cell (CD8⁺T cell) in blood samples. A total of 24 mice injected with recombinant adeno-associated virus 8 carrying 1.3 copies of HBV genome via tail vein were randomly divided into 3 groups: control group (dimethylsulfoxide), PGE2 group (stable analog of PGE2) and PGE2 receptor antagonist group (PGE2 receptor antagonist). The levels of hepatitis B surface antigen (HBsAg), HBV deoxyribonucleic acid (DNA) and pregenomic ribonucleic acid (pgRNA) in mouse serum of the 3 groups were detected by kit and real-time quantitative polymerase chain reaction. The function of CD8⁺ T cell in the liver were detected by flow cytometry. Results The serum level of PGE2 in CHB patients was significantly higher than that in HP (877.2 ± 43.27 vs. 201.3 ± 13.38, P<0.05). In patients with high PGE2, the serum levels of HBV DNA, ALT, AST were significantly higher than those in patients with low PGE2 (1.84 ± 0.161 vs. 0.92 ± 0.143, 722.64 ± 33.081 vs. 246.95 ± 26.629, 514.20 ± 13.427 vs. 183.07 ± 12.259, P<0.05), and the expression of T cell immunoglobulin and mucin domain 3 in blood CD8⁺ T cells (Tim3) was significantly higher (18.64 ± 2.051 vs. 15.12 ± 2.265, P<0.05), the expression of granzyme B was significantly lower than that in patients with low PGE2 (0.29 ± 0.102 vs. 0.38 ± 0.095, P<0.05). Compared with the control group, the serum levels of HBsAg, HBV DNA and pgRNA in the PGE2 group were significantly higher (5.57 ± 0.941 vs. 4.51 ± 0.662, 0.58 ± 0.073 vs. 0.42 ± 0.049, 0.57 ± 0.069 vs. 0.40 ± 0.051, P<0.05), the expression of Tim3 in liver CD8⁺ T cells was significantly higher (25.45 ± 3.412 vs. 12.63 ± 2.313, P<0.05), and the expression of tumor necrosis factor-α and interferon-γ was significantly lower in the PGE2 group (21.50 ± 3.139 vs. 27.36 ± 3.841, 15.23 ± 2.105 vs. 24.81 ± 2.595, P<0.05). PGE2 receptor antagonism has the opposite effect.Conclusion PGE2 is highly expressed in serum of CHB patients, which promotes replication of HBV and depletion of T cell. And blocking of PGE2 can not only restore T cell function but also reduce HBV replication.

Autoimmune Liver Disease

Study of budesonide or prednisone combined with azathioprine in the treatment of autoimmune hepatitis

MA Chun-yan, LU Ya-ni, DU Feng, HE Ya-li, CHANG Ting-ting.

2020, 25(3):  282-284. 

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Objective To compare the efficacy of budesonide combined with azathioprine and prednisone combined with azathioprine in the treatment of autoimmune hepatitis (AIH).Methods A total of 90 patients with AIH admitted to our hospital from January 2015 to January 2018 were randomly divided into the budesonide group and the prednisone group, 45 cases each. The budesonide group was treated with budesonide plus azathioprine, and the prednisone group was treated with prednisone plus azathioprine. Both groups were treated continuously for 2 years. The total clinical remission rate, serum ALT, AST, ALP, γ-GT levels and the total incidence of adverse reactions were compared between the 2 groups. Results The overall clinical remission rate of the budesonide group was 88.89%, which was significantly higher than 71.11% of the prednisone group (P<0.05). The levels of serum ALT, AST, ALP and γ-GT in the 2 groups after 2 years of treatment were significantly lower than those before treatment (P<0.05). The levels of ALT, AST, ALP and γ - GT in the budesonide group were (27.42 ± 5.36) U/L, (29.97 ± 4.52) U/L, (88.11 ± 14.32) U/L, (49.52 ± 7.62) U/L, respectively, which were significantly lower than those in the prednisone group (P<0.05). The overall incidence of adverse reactions during treatment in the budesonide group was 15.56%, which was significantly lower than 35.56% of the prednisone group (P<0.05).Conclusion Budesonide combined with azathioprine in the treatment of AIH can achieve higher remission rate, more obvious improvement of biochemical indicators, and fewer adverse reactions, which is better than prednisone combined with azathioprine.